Genetic analysis of the spinal motor circuits

(1) Which neuronal subtypes in the spinal cord make synaptic connections with the motor neurons? 

(2) What is the precise function of these neuronal subtypes in the generation of appropriate motor output during locomotion? 

The main driving force behind our experimental approach is the availability of a number of genetic markers and regulatory sequences that are specific to neuronal subtypes within the spinal cord. In combination with a novel approach for reversibly silencing  neurons by transgene expression, we hope to generate information about the function of many different spinal interneurons in the generation of motor patterns. These data will provide a map of the synaptic information flow, much as blocking activity of specific enzymes was used to understand complex, often interwoven, metabolic pathways. 

Research techniques: 

 (1) Analysis of gene expression 
 (2) Generation of transgenic mice and in-ovo electroporation for gene misexpression 
 (3) Morphological analysis of neuronal connections 
 (4) Physiological evaluation of the motor function

J. Thaler, K. Harrison, K. Sharma, K. Lettieri , J. Kerl and S.L. Pfaff: (1999)  Appropriate motor neuron specification and axon pathfinding is dependent on homeodomain factor HB9: A repressor of interneuron identity. Neuron, 23:675-687. 

K. Sharma, H.Z. Sheng, K. Lettieri, H. Li, A. Karavanov, S. Potter, H. Westphal and S.L. Pfaff.  (1998) LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons. Cell, 95:817-828. 

N. Takuma, H.Z. Sheng, Y. Furuta, J.M. Ward, K. Sharma, B.L.M. Hogan, S.L. Pfaff, H. Westphal, S. Kimura and K.A. Anderson.  (1998)  Formation of Rathke's pouch requires dual induction from the diencephalon. Development, 125:4835-4840. 

K. Sharma and E. Frank.  (1998)  Sensory axons are guided by local cues in the developing dorsal spinal cord. Development, 125: 635-643. 

K. Sharma,  Z. Korade and E. Frank.  (1995)  Late-migrating neuroepithelial cells from the spinal cord differentiate into sensory ganglion cells and melanocytes. Neuron, 14:143-152. 

K. Sharma, Z. Korade and E. Frank.  (1994)  Central projections of sensory axons wait for development of guidance cues in the spinal cord. Development, 120:1315-1323.